The proposed research project is designed to elucidate some of the mechanisms underlying the kinds of change in function that occur in neuromuscular junctions during development or degeneration, and thereby the research will also increase understanding of synapse function in general. The study is restricted to the processes of transmitter release and activation of the post synaptic response. The approach calls for observing identified synapses in different states of change (development of degeneration) or for comparing two slightly different synapses in the same animal under the same experimental paradigm. Combined electrophysiological and ultrastructural techniques will be employed to record the changes in activity and correlated changes in structure of specified junctions. The physiological parameters are endplate potential amplitude, miniature endplate potential amplitude and frequency, and facilitation properties. The structural features are those thought to be associated with transmitter release and receptor activation: the "active zone"; the aggregation of synaptic vesicles and the plasmalemmal deformations that indicate their fusion with the membrane; the coated vesicles and coated pits that are associated in activity induced endocytosis; and the postsynaptic specializations. By comparing structure with function at different stages, I hope to be able to correlate or demonstrate lack of correlation between particular functions and particular structural features, e.g.: the post synaptic particle specialization with receptor function and distribution; the total length or lengths of each active zone with endplate potential amplitude and/or facilitation properties; and finally the possible dependent interrelationship of the pre- or post- synaptic particle specialization on nerve activity.